M 6A-related genes characterization in hepatocellular cancer identifies prognostic relevant gene signatures

Abstract Background Hepatocellular carcinoma (HCC) is among the most common types of cancers that threat the public health worldwide. N6-methyladenosine (m6A) RNA methylation, associated with cancer initiation and progression, is dynamically regulated by m6A RNA methylation associated genes. However, little is known about the expression status and the prognostic value of m6A associated genes in HCC. This study aimed to identify the expression profiling pattern and clinical significance of m6A-related genes in HCC. Methods The Cancer Genome Atlas (TCGA-LIHC), the Gene Expression Omnibus (GSE14520) and the Human Protein Atlas (HPA) databases were gathered for this study. Consensus clustering analysis was performed to identify the clusters of HCC with different clinical outcome. A prognostic signature built by the least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to discover subtypes correlated with different clinical outcomes of HCC patients and the differences between subgroups were characterized in terms of epigenetic dysregulation and somatic mutation frequencies. Results Most of the m6A-related genes were upregulated and involved with the prognosis and malignancy of HCC. A four-gene prognostic signature revealed two HCC subtypes (namely, risk-high group and risk-low group) that correlated with different clinical outcomes. Patients in risk-high group were accompanied with much more epigenetic silencing and significant mutation at TP53 and FLG, while ALB were mutated frequently for risk-low group. Conclusion Our characterization tightly links the expression of m6A genes with clinical outcomes of HCC, providing valuable molecular-level information that points to decoding heterogeneity, guiding personalized management and treatment of HCC patients.